Patent
Regioselective palladium catalyzed synthesis of benzimidazoles and azabenzimidazoles
| العنوان: | Regioselective palladium catalyzed synthesis of benzimidazoles and azabenzimidazoles |
|---|---|
| Patent Number: | 8,188,282 |
| تاريخ النشر: | May 29, 2012 |
| Appl. No: | 12/353271 |
| Application Filed: | January 14, 2009 |
| مستخلص: | The present invention relates to a process for the regioselective synthesis of compounds of the formula I, [chemical expression included] wherein R0; R1; R2; R3; R4; R5; A1; A2; A3; A4, Q and J have the meanings indicated in the claims. The present invention provides a direct palladium catalyzed, regioselective process to a wide variety of unsymmetrical, multifunctional N-substituted benzimidazoles or azabenzimidazoles of formula I starting from 2-halo-nitroarenes and N-substituted amides useful for the production of pharmaceuticals, diagnostic agents, liquid crystals, polymers, herbicides, fungicidals, nematicidals, parasiticides, insecticides, acaricides and arthropodicides. |
| Inventors: | Alonso, Jorge (Mannheim, DE); Lindenschmidt, Andreas (Frankfurt, DE); Nazare, Marc (Frankfurt, DE); Halland, Nis (Frankfurt, DE); Rkyek, Omar (Frankfurt, DE); Urmann, Matthias (Frankfurt, DE) |
| Assignees: | Sanofi-Aventis (Paris, FR) |
| Claim: | 1. A process for preparing a compound of formula I [chemical expression included] or a stereoisomeric form of the compound of formula I, or a mixture of these forms in any ratio, or a physiologically tolerated salt of a compound of formula I, wherein A1, A2, A3, A4 are each carbon to form together with the two carbon atoms in formula I a stable aromatic ring; Q is —(C 1 -C 6)-alkylene, wherein the alkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 3 -C 8)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 6 -C 14)-aryl, wherein the aryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; or —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; J is —(C 1 -C 6)-alkylene, wherein the alkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 3 -C 8)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 6 -C 14)-aryl, wherein the aryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; or —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; R0, R1, R2, R3, R4 and R5 are independent of one another identical or different and are a) hydrogen atom, b) —(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, c) halogen, d) phenyloxy-, wherein the phenyloxy is unsubstituted or substituted one to three times by R13, e) —(C 1 -C 3)-fluoroalkyl, f) —N(R10)-(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, g) —(C 6 -C 14)-aryl, wherein the aryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, h) —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, i) —(C 3 -C 8)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, or j) a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, k) —O—CF 3 , l) —O—(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, m) —NO 2 , n) —CN, o) —OH, p) —C(O)—R10, q) —C(O)—O—R11, r) —C(O)—N(R11)-R12, s) —N(R11)-R12, t) —N(R10)-SO 2 —R10, v) —S—R10, w) —SO 1 R10, wherein n is 1 or 2, x) —SO 2 —N(R11)(R12) or y) at least one of R1, R2, R3 or R4 are absent in case one or more of A1, A2, A3 or A4 is a nitrogen atom, or R1 and R2, R2 and R3 or R3 and R4 form together with the atoms which they are attached to a 5- or 8-membered ring, containing 0, 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said ring is unsubstituted or substituted one, two, three or four times by R14, R10 is hydrogen atom, —(C 1 -C 3)-fluoroalkyl or —(C 1 -C 6)-alkyl, R11 and R12 are independently of one another identical or different and are a) hydrogen atom, b) —(C 1 -C 6)-alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, c) —(C 6 -C 14)-aryl-, wherein the aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13 or R13 is halogen, —NO 2 , —CN, ═O, —OH, —(C 1 -C 8)-alkyl, —(C 1 -C 8)-alkoxy, —CF 3 , phenyloxy-, —C(O)—O—R17, —C(O)—N—(R17)-R18, —N(R17)-R18, —C(O)—R10, —N(R10)-SO 2 —R10, —S—R10, —SO n —R10, wherein n is 1 or 2, —SO 2 —N(R17)-R18, —(C 6 -C 14)-aryl, wherein the aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, —(C 3 -C 8)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, or a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, R14 is halogen, —OH, ═O, —CN, —CF 3 , —(C 1 -C 8)-alkyl, —(C 1 -C 4)-alkoxy, —NO 2 , —C(O)—OH, —NH 2 , —C(O)—O—(C 1 -C 4)-alkyl, —(C 1 -C 8)-alkylsulfonyl, —C(O)—NH—(C 1 -C 8)-alkyl, —C(O)—N [(C 1 -C 8)-alkyl] 2 , —C(O)—NH 2 , —S—R10, —N(R10)-C(O)—NH—(C 1 -C 8)-alkyl, or —N(R10)-C(O)—N[(C 1 -C 8)-alkyl] 2 , R17 and R18 are independently of one another identical or different and are a) hydrogen atom, b) —(C 1 -C 6)-alkyl, c) —(C 6 -C 14)-aryl- or d) —(C 4 -C 14)-heteroaryl, said process comprising reacting a compound of formula II [chemical expression included] wherein R1, R2, R3, R4, A1, A2, A3 and A4 are as defined in formula I and X is Cl, Br, I, triflate or nonaflate, with a compound of formula III [chemical expression included] wherein Q, J, R0 and R5 are as defined in formula I, in the presence of a palladium catalyst, a base, a ligand and an aprotic solvent to give a compound of formula IV [chemical expression included] and converting the compound of formula IV into a compound of formula I in the presence of a reducing reagent and a second solvent, and optionally converting the compound of formula I to a physiologically tolerated salt thereof. |
| Claim: | 2. The process according to claim 1 , wherein a compound of formula I is prepared, wherein A1, A2, A3 and A4 form together with the two carbon atoms in formula I a benzene, Q is —(C 1 -C 6)-alkylene, wherein the alkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 3 -C 6)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; phenyl, wherein the phenyl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; or —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is selected from acridinyl, azaindole (1H-pyrrolopyridinyl), azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 3,3-dioxo[1,3,4]oxathiazinyl, 6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, indanyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, oxetanyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, and wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; J is —(C 1 -C 6)-alkylene, wherein the alkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; —(C 3 -C 6)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14; phenyl, wherein the phenyl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; or —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13; R0, R1, R2, R3, R4 and R5 are independent of one another identical or different and are a) hydrogen atom, b) F, c) Cl or Br, d) —(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, e) —(C 1 -C 3)-fluoroalkyl, f) phenyl, wherein the phenyl is unsubstituted or substituted one to three times by R13, g) —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, h) —(C 3 -C 8)-cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, i) a 3- to 7-membered cyclic residue selected from azepine, azetidine, aziridine, azirine, 1,4 diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine, morpholine, 1,2-oxa-thiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxetan, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydrofuran, tetrahydropyran, tetrahydropyridine, tetrazine, tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, and is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13, j) —O—CF 3 , k) —O—(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, l) —N(R10)-(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or substituted one to three times by R13, m) —CN, n) —OH, o) phenyloxy-, wherein the phenyloxy is unsubstituted or substituted one to three times by R13, p) —C(O)—O—R11, q) —C(O)—N(R11)-R12, r) —N(R11)-R12, s) —N(R10)-SO 2 —R10, t) —S—R10, v) —SO n —R10, wherein n is 1 or 2, w) —SO 2 —N(R11)-R12, x) —C(O)—R10 or y) at least one of R1, R2, R3 or R4 are absent in case one or more of A1, A2, A3 or A4 is a nitrogen atom, R10 is hydrogen atom, —(C 1 -C 3)-fluoroalkyl or —(C 1 -C 6)-alkyl, R11 and R12 are independently of one another identical or different and are a) hydrogen atom, b) —(C 1 -C 4)-alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, c) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13 or R13 is F, Cl, —CN, ═O, —OH, —(C 1 -C 8)-alkyl, —(C 1 -C 8)-alkoxy, —CF 3 , phenyloxy-, —C(O)—R10, —C(O)—O—R17, —C(O)—N(R17)-R18, —N(R17)-R18, —N(R10)-SO 2 —R10, —S—R10, —SO n —R10, wherein n is 1 or 2, —SO 2 —N(R17)-R18, phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, —(C 4 -C 14)-heteroaryl, wherein the heteroaryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, —(C 3 -C 6)-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, or a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, which is unsubstituted or mono-, di- or trisubstituted independently of one another by R14, R14 is F, Cl, —OH, ═O, —CN, —CF 3 , —(C 1 -C 8)-alkyl, —(C 1 -C 4)-alkoxy, —C(O)—OH, —NH 2 , —C(O)—O—(C 1 -C 4)-alkyl, —(C 1 -C 8)-alkylsulfonyl, —C(O)—NH 2 , —S—R10, —C(O)—NH—(C 1 -C 8)-alkyl, —C(O)—N[(C 1 -C 8)-alkyl] 2 , —N(R10)-C(O)—NH—(C 1 -C 8)-alkyl or —N(R10)-C(O)—N[(C 1 -C 8)-alkyl] 2 , R17 and R18 are independently of one another identical or different and are a) hydrogen atom, b) —(C 1 -C 4)-alkyl, c) phenyl or d) —(C 4 -C 14)-heteroaryl and X is Cl, Br or I. |
| Claim: | 3. The process according to claim 1 , wherein a compound of formula I is prepared, wherein A1, A2, A3 and A4 form together with the two carbon atoms in formula I a benzene, Q is phenyl, which is unsubstituted or substituted by R13, —(C 1 -C 6)-alkylene or pyridyl, R0, R1, R2, R3, R4 and R5 are independent of one another identical or different and are a) hydrogen atom, b) F, c) Cl, d) Br, e) —(C 1 -C 4)-alkyl, f) —(C 3 -C 6)-cycloalkyl g) phenyl, h) —O—(C 1 -C 4)-alkyl, i) —C(O)—O—R11, j) —CN, k) —C(O)—R10 or l) at least one of R1, R2, R3 or R4 are absent in case one or more of A1, A2, A3 or A4 is a nitrogen atom, R10 is hydrogen atom or —(C 1 -C 4)-alkyl, R11 is hydrogen atom or —(C 1 -C 4)-alkyl, R13 is —C(O)—O—R17, R14 is Cl, F, —(C 1 -C 8)-alkyl or —C(O)—O—(C 1 -C 4)-alkyl, R17 is hydrogen atom or —(C 1 -C 4)-alkyl and X is Cl, Br or I. |
| Claim: | 4. The process according to claim 1 , wherein one of the following compounds of formula I is prepared: 5-Chloro-2-methyl-1-phenyl-1H-benzimidazole; 2-Methyl-1-phenyl-1H-benzimidazole; 7-Chloro-2-methyl-1-phenyl-1H-benzimidazole; 2,7-Dimethyl-1-phenyl-1H-benzimidazole; 5-Methoxy-2-methyl-1-phenyl-1H-benzimidazole; 2-Methyl-1-phenyl-1H-benzimidazole-5-carbaldehyde; 1,2-Diphenyl-1H-benzimidazole; 1-Phenyl-2-pyridin-3-yl-1H-benzimidazole; 1-Phenyl-2-tridecyl-1H-benzimidazole; 1,2-dimethyl-1H-benzimidazole; 2-Methyl-1-phenethyl-1H-benzimidazole; 2-Methyl-1-pyridin-2-yl-1H-benzimidazole; 5-(1-Phenyl-1H-benzoimidazol-2-yl)-pentanoic acid methyl ester; 2-(5-Chloro-pentyl)-1-phenyl-1H-benzimidazole; 1-(4-Methoxy-phenyl)-2-methyl-1H-benzimidazole; 4-(2-Methyl-benzoimidazol-1-yl)-benzonitrile; 2-Ethoxy-4-(2-methyl-benzoimidazol-1-yl)-benzoic acid methyl ester, 2,4-Dimethyl-1-phenyl-1H-benzimidazole; 5-cyano-2-methyl-1-phenyl-1H-benzimidazole; 2-Methyl-1-pyridin-2-yl-1H-benzimidazole; 5-(2-Heptyl-benzoimidazol-1-yl)-pentanoic acid tert-butyl ester; 6-(2-Methyl-benzoimidazol-1-yl)-hexanoic acid methyl ester; or 2-Cyclopentylmethyl-1-(2-methyl-butyl)-1H-benzimidazole-5-carboxylic acid methyl ester. |
| Claim: | 5. The process according to claim 1 , wherein the palladium catalyst is selected from the group consisting of Pd-alkanoates, Pd-alkanoate complexes, Pd-acetonates, Pd-halides, Pd-halide complexes and Pd-phosphine complexes. |
| Claim: | 6. The process according to claim 5 , wherein the palladium catalyst is selected from the group consisting of palladium (II) acetate, palladium (II) trifluoroacetate, tris(dibenzylidene-acetone)dipalladium(0), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct, palladium (II) chloride, 2,2′-bis(diphenylphosphino)-1,1′-binaphthylpalladium(II) chloride, acetato(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium(II), (1,2-Bis(diphenylphosphino)ethane)dichloropalladium(II), Bis[1,2-bis(diphenylphosphino)ethane]palladium (0), [(2S,3S)-Bis(diphenyl-phosphino)butane] [eta3-allyl]palladium(II) perchlorate, and 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene(1,4-naphthoquinone)palladium (0) dimer. |
| Claim: | 7. The process according to claim 5 , wherein the palladium catalyst is palladium (II) acetate, 2,2′-bis(diphenylphosphino)-1,1′-binaphthylpalladium(II) chloride or palladium (II) trifluoroacetate. |
| Claim: | 8. The process according to claim 1 , wherein the base is selected from the group consisting of carbonates, phosphates, fluorides, alkoxides and hydroxides with a metal as counterion. |
| Claim: | 9. The process according to claim 8 , wherein the base is selected from the group consisting of potassium carbonate, potassium phosphate and cesium carbonate. |
| Claim: | 10. The process according to claim 1 , wherein the ligand is selected from the group consisting of (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene, 4,5-Bis(diphenyl-phosphino)-9,9-dimethylxanthene, (R)-(−)-1-[(5)-2-(diphenylphosphino) ferrocenyl]ethyldicyclohexylphosphine, 1,2-Bis(diphenylphosphino)ethane, 1,3-Bis(diphenylphosphino)propane, (R)-(−)-1-[(S)-2-(Dicyclohexylphosphino)-ferrocenyl]ethyldi-tert-butylphosphine, (R)-(+)-1,1′-Bis(diphenylphosphino)-2,2′-bis(N,N-diiisopropylamido)ferrocene, (S,S)-1-[1-(Di-tert-butylphosphino)ethyl]-2-(diphenylphosphino)ferrocene, (1R,2R)-(+)-1,2-Diaminocyclohexane-N,N′-bis(2-diphenylphosphino-1-naphtoyl, (−)-1,2-Bis((2S,5S)-2,5-diiso-propylphospholano)-benzene, Bis[(2-diphenylphosphino)phenyl]ether, (5)-(+2,T-Bis(di-para-tolylphosphino)-1,1′-binaphyl, 4,5-Bis(bis(3,5-bis(trifluoromethyl)phenyl)-phosphino)-9,9-dimethylxanthen, 2,2′-bis[(2′,4′,6′-triisopropyl)dicyclohexyl-phosphino]biphenyl and 2,2′-bis(di-tert-butylphosphino)biphenyl, tri-tert-butylphosphine. |
| Claim: | 11. The process according to claim 10 , wherein the ligand is 2,2′-bis(diphenyl-phosphino)-1,1′-binaphthalene or 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene. |
| Claim: | 12. The process according to claim 1 , wherein the aprotic solvent is selected from the group consisting of benzene, toluene, xylene, mesitylene, acetonitrile, tetrahydrofuran, dimethylformamide, n-methylpyrrolidinone, dimethylacetamide, dimethylsulfoxide, (2-methoxyethyl)ether and pyridine. |
| Claim: | 13. The process according to claim 12 , wherein the aprotic solvent is selected from the group consisting of benzene, mesitylene and toluene. |
| Claim: | 14. The process according to claim 1 , wherein the reaction between the compound of formula II and formula III is carried out at a temperature in the range of 60° C. to 150° C. |
| Claim: | 15. The process according to claim 14 , wherein said temperature is the range of 70° C. to 90° C. |
| Claim: | 16. The process according to claim 1 , wherein the second solvent is selected from the group consisting of methanol, ethanol, propanol, acetic acid, methylene chloride, dimethylformamide, tetrahydrofuran, pyridine, p-xylene, ethylacetate, benzene, toluene, xylene, mesitylene and acetonitrile. |
| Claim: | 17. The process according to claim 16 , wherein the second solvent is selected from the group consisting of methanol, ethanol, acetic acid, methylene chloride, dimethylformamide, pyridine and p-xylene. |
| Claim: | 18. The process according to claim 1 , wherein the reducing reagent is selected from the group consisting of H 2 /Raney-N 1 , H 2 /Pd—C, H 2 /PtO 2 , H 2 /Ru, NaBH 4 /NiCl 2 , NaBH 4 /FeCl 2 , H 3 PO 2 /Pd—C, Sn/HCl, SnCl 2 /HCl, Fe/HOAc, Fe/HCl, FeSO 4 /HCl, Fe/FeSO 4 , Zn/HCl, Na 2 S, and Na 2 S 2 O 4 . |
| Claim: | 19. The process according to claim 1 , wherein the reduction reaction of the compound of formula IV to the compound of formula I is carried out at a temperature in the range of 80° C. to 140° C. |
| Claim: | 20. The process according to claim 19 , wherein said temperature is in the range of 110° C. to 120° C. |
| Current U.S. Class: | 546/118 |
| Patent References Cited: | 6124323 September 2000 Bigge et al. 2005/0203078 September 2005 Priepke et al. WO 2006/069807 July 2006 |
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| Primary Examiner: | Chandrakumar, Nizal |
| Attorney, Agent or Firm: | Scully, Scott, Murphy & Presser, P.C. |
| رقم الانضمام: | edspgr.08188282 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |